Excessive insulin therapy: biochemical effects and clinical repercussions. Current concepts of counterregulation in...

Excessive doses of insulin cause unstable or "brittle" diabetes in many diabetic patients. Chronic insulin overtreatment can be very difficult to recognize because nocturnal hypoglycemia may be infrequent and asymptomatic. Recognition of subtle historical clues and informed interpretation of laboratory results facilitate diagnosis. Some insulin-treated diabetic patients fail to respond to severe nocturnal hypoglycemia with the acute secretion of counterregulatory hormones. "Rebound" morning hyperglycemia coincides with decreased plasma free insulin levels and the normal diurnal rise in plasma cortisol levels. Moreover, these patients show hyperresponsiveness to counterregulatory hormones (particularly cortisol and epinephrine), exaggerated hepatic glucose production, and prolonged impairment of peripheral and splanchnic glucose disposal. When chronic overtreatment is suspected, insulin therapy must be modified to better approximate physiologic needs for glucose disposal. Until fundamental problems of insulin replacement are solved, chronic insulin overtreatment should be considered as one cause of unstable diabetes.